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Title: Heterogeneity in untreated, stressed and drug-tolerant cells: insights into the evolution of cancer resistance

Authors: Bhagya K. Wijayawardena; Gopinath Sivasankaran; Lang Li

Addresses: Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA ' Indiana University School of Informatics and Computing, Indianapolis, Indiana 46202, USA ' Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA

Abstract: The evolution of cancer is a Darwinian process, the composition of cancer cell population varying with time, especially after chemotherapy. Such changes occurring in the genetic landscape of tumours are possibly responsible for the chemotherapeutic resistance. Due to the recent advances in single cellular sequencing, the evolution of cancers can be monitored at the single cellular resolution. We reanalysed a previously published dataset composed of single cell RNAseq data, collected before, during and after the establishment of Paclitaxel tolerance, to identify single cell heterogeneity. We used gene expression analysis, gene expression rank correlation analysis, pathway analysis and mutation analysis to identify within group variations of cancer cells after chemotherapy. We identified a decrease in cancer cell within group diversity during the transition to drug-tolerance. Additionally, we observed high mutation rate in stressed single cells, which suggests genetic instability of cancer cells that could ultimately result in the development of drug resistance. Our analysis carries significant implications for developing personalised and efficient therapeutics against cancer.

Keywords: single cell RNAseq; drug resistance; paclitaxel; chemotherapy; tumour; drug 18 tolerance; Illumina HiSEq; MDA-MB-231.

DOI: 10.1504/IJCBDD.2018.090846

International Journal of Computational Biology and Drug Design, 2018 Vol.11 No.1/2, pp.23 - 38

Available online: 23 Mar 2018 *

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